Steroids are macromolecular, non-volatile and thermosensitive organic compounds with a complicated structure. They are used for many special purposes: as pharmaceuticals, additives in foodstuffs, cosmetic products, etc. They are often produced on a small scale, and the same multipurpose reactor is used in steroid syntheses for various reactions, such as hydrogenation, oxidation, reduction and esterification.
Steroids are a group of compounds with a similar structure. They are commonly present in plants and animals and include, for example, sterols, vitamin D, bile acids and sex hormones. The structure of steroids is based on the following 1,2-cyclopentenofenanthrene ring system: ##STR1##
Sterols are steroids whose structure contains an OH group. Sterols are crystalline C.sub.26 -C.sub.30 compounds, and they contain an aliphatic side chain at C.sub.17. Sterols occur in the nature either as free sterols or as esters of higher fatty acids. Sterols can be isolated from the non-saponifiable moiety of fats and oils. The best known animal sterol (zoosterol) is cholesterol. The best known plant sterols (phytosterols) are stigmasterol, sitosterol and ergosterol (yeast sterol). The structure of cholesterol is illustrated by the following formula: ##STR2##
The stereochemistry of the substituents at carbon atoms 3 and 10 is important for the hydrogenation of the .DELTA..sup.5 -double bond. If the hydroxyl group at C.sub.3 and the methyl group at C.sub.10 are both above the ring, they are at a cis-position in relation to each other. In steroids, a group of substituents above the ring is indicated with .beta., whereas a group of substituents below the ring is indicated with .alpha.. In all plant sterols, the hydroxyl and methyl group are at a .beta.-position.
The structure of sitosterol differs from that of cholesterol only in that in sitosterol there is an ethyl group attached to C.sub.24. The double bond of sitosterol and cholesterol is called a .DELTA..sup.5 -bond. Cholesterol is also known by the name of 5-cholesten-3.beta.-ol, and sitosterol by the name of 24.alpha.-ethyl-5-cholesten-3.beta.-ol.
Catalytic hydrogenation is a common intermediate step in steroid syntheses, for example. It is used for reducing various functional groups or for hydrogenating double bonds. Whether a hydrogenation is successful depends on whether the product is stereochemically correct. If the product is stereo-specifically incorrect, it is not suitable for further syntheses or for the actual application. The hydrogenation process of the invention is used for preparing steroids in which the H-atom at C.sub.5 is at an .alpha.-position.
According to the prior art, steroids have been hydrogenated by means of nickel black, Raney nickel, and nickel catalysts attached to inorganic supports. The activity of nickel metal has, however, not been sufficient for hydrogenating steroid double bonds. Steroids have also been hydrogenated with noble metal catalysts, particularly Pd- and Pt-catalysts. Hydrogenations have been carried out by the use of metal blacks, or noble metal catalysts bound to inorganic supports or to activated carbon. The best conversions of the starting material have been achieved with noble metal catalysts bound to activated carbon, particularly with the Pd/C-catalyst. It is generally known that the problems with the use of such a catalyst have been the separation of particulate catalyst powder from the reaction mixture after hydrogenation, the inflammability of the catalyst, and the fact that the catalyst is not recyclable.
Until the 1960's, the catalyst most commonly used for hydrogenating the .DELTA..sup.5 -double bond of steroids was platinum. In syntheses, platinum has been used in the form of Adams Pt-oxide. The Adams Pt-oxide is a hydrogenation catalyst prepared in situ by reducing platinous dioxide with hydrogen to platinum metal.
At the end of the 1960's, it was found that the most efficient catalyst in hydrogenation of steroid double bonds was palladium. Hydrogenation of cholesterol with a Pd/C-catalyst in ethanol at room temperature and under a normal atmosphere gave a cholestanol yield of 85 to 95%. This is a better yield than has been obtained with Pt-oxide in ethyl acetate and cyclohexane, and much better than has been obtained with Pt-oxide in acetic acid.
Cholesterol has been hydrogenated with Pt, Rh, Ir, Ru, Os, and Pd metals in a competing reaction with .alpha.-pinene. The reaction rate of cholesterol in relation to .alpha.-pinene was 1.2 with Pd, whereas with Os the reaction could not be detected, and with the other metals the relative reaction rate was of the order of 0.12 to 0.16. The strong reaction of steroids with a Pd-catalyst is a result of their high adsorption to the surface of palladium. Particularly the .alpha.-surface of steroids has a high ability to adsorb to palladium.
Pt-oxide can be used if the hydrogenolysis of other functional groups is to be avoided in the hydrogenation of steroid double bonds. Raney nickel or platinum is recommended when the migration of the double bond presents a problem. The pure 5.alpha.-form has been obtained in the hydrogenation of a .DELTA..sup.5 -double bond by the use of Raney nickel, Pt-oxide or copper chrome oxide.
Hydrogenation of unsaturated oils and fats involves hydrogenation of numerous double bonds in an aliphatic chain. The hydrogenation reaction of fats and oils is complicated because of simultaneously occurring isomerization of unsaturated bonds. Vegetable oils are triglycerides of fatty acids and contain one, two, three or even more unsaturated bonds in each fatty acid.
The most important acids for hydrogenation are, for example, linolenic, linolic and oleic acid, all of which contain 18 carbon atoms. Linolenic acid is a fatty acid containing three double bonds: one at the 9th, 12th and 15th bond. Linolic acid contains two double bonds: one at the 9th and 12th bond. Oleic acid, in turn, contains one double bond at the 9th bond. The end product of the hydrogenation of these fatty acids is stearic acid, which is a saturated molecule containing 18 carbon atoms.
Hydrogenation is a way of converting liquid oils into semi-solid plastic fats suited for the production of fat products and margarines. Hydrogenation also has other desirable properties: it improves the stability and colour of the fat, for example.
Metals that are catalytically active in the hydrogenation of double bonds of fatty acid molecules include Fe, Co, Ni, Pd, Pt, Cu, Ag and Au. Nickel-based catalysts have been used most in processes for hydrogenating oils. The problem with the use of a nickel catalyst has been insufficient selectivity. In addition, nickel catalysts have not been suitable for selective hydrogenation from linolenic acid to linolic acid.
It is known that the aim in catalyst studies has long been to develop a catalyst that possesses the advantages of both a homogeneous and a heterogeneous catalyst. A homogeneous catalyst, i.e. a liquid catalyst in liquid phase hydrogenation, gives almost always better selectivity and activity than a heterogeneous catalyst, i.e. a solid catalyst in hydrogenation, which in turn has better separability. Although it is easier to separate a heterogeneous catalyst from a reaction mixture after hydrogenation than a homogeneous one, it is often still too complicated, since in order to obtain sufficient activity, it is necessary to use particulate catalyst powders. The aim in developing polymer-bound catalysts has been to combine the advantages of homogeneous and heterogeneous catalysis.
Polymer-bound catalysts have many advantages. They have higher activity than conventional heterogeneous catalysts, since the active sites of the catalyst are isolated from each other, and ligand-bridged complexes are not formed. Polymer-bound catalysts also have better selectivity on account of the larger steric environment. In addition, the catalyst losses are smaller than with conventional catalysts.
Polymer-bound catalysts are clearly more expensive than conventional catalysts, wherefore the support must be selected such that the catalyst can be recycled. The support must also be mechanically strong in order for the catalyst to endure even vigorous mixing. The physical structure of the support must be suitable to allow as many functional groups as possible to come into contact with the reaction mixture. In addition, the microenvironment of the support must be of the right kind and suitable for the reaction: it should possess, for example, the correct polarity, hydrophilicity and microviscosity.
In recent years, crosslinked polystyrene resins have been commonly used as supports for transition metal catalysts. However, their use is problematic, wherefore resin-bound catalysts cannot be used in industrial applications. The reaction rate is to a great extent dependent on the solvent which swells the polymer and allows the reactants access to the active sites of the catalyst. In addition, differences in polarity and changes in the size of the reactants may prevent diffusion in the resin.
Because of the problems with polystyrene resins, new polymer support materials have been searched for in recent years. Polyolefins, particularly polyethylene and polypropylene, used as support materials, have proved to be promising. The Wilkinson homogeneous catalyst, for example, is attached to a polyethylene crystal and to a microporous polyethylene hollow fibre by chemical methods. The process for preparing these catalysts is complicated, and therefore not suitable for production of catalysts on a large scale.
A catalyst is deactivated in use, when its activity or selectivity decreases from the original level. The deactivation may result from poisoning, fouling or sintering of the catalyst, or from the loss of the active component. Sulphur is one of the most common substances which poison metal catalysts.
Regeneration is a treatment for restoring the original activity of a catalyst.
Regeneration of a deactivated polymer-supported metal catalyst has not been reported in the prior art.